Carborane derivatives as inhibitors of human carbonic anhydrase isoenzymes

INTRODUCTION:

Human carbonic anhydrases (CAs) play important roles in many pathological processes and several CA isoenzymes thus represent diagnostic and therapeutic targets. The development of certain isoform-specifi c sulfonamide inhibitor is still an important task in current medicine.

TECHNOLOGY (INVENTION) DESCRIPTION:

We have developed unique selective CAIX inhibitors with anticancer properties based on carborane scaffold to structure-assisted design of novel and original inhibitors targeting therapeutically relevant isoenzymes of human carbonic anhydrase.

ADVANTAGES OVER EXISTING SOLUTIONS:

Novelty, in brief, is represented by the intended elaboration of carborane, heteroborane and metallaborane compounds as active-site inhibitors of CA isoenzymes. All currently used inhibitors anhydrase inhibitors contain a sulfonamide or a sulfamate moiety connected to so called ‘ring structure’ which is usually a 5- or 6-membered aromatic ring or conjugated ring system containing nitrogen, oxygen, and/ or sulfur heteroatoms. The ‘ring structure’ bears characteristics or functionality which modulates the affi nity toward certain CA isoform. The use of three-dimensional boron cluster is a novel approach in development of isoform-specifi c CA inhibitors. Selected sulfamides incorporating cluste

DEVELOPMENT STATUS (STAGE):

Laboratory scale, data on cell lines, crystal structure, limited ADME/Tox data, in vivo pharmacology and pharmacodynamic

PUBLICATIONS:

IP PROTECTION STATUS:

Patent protection: WO 2013/060307 EP 2771015 US 2014/303390

TECHNOLOGY / IP OWNERS :

Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences Institute of Molecular Genetics, Czech Academy of Sciences Institute of Inorganic Chemistry, Czech Academy of Sciences Palacky University Olomouc